Insulin resistance is a common characteristic of the diabetic state and of several other pathological conditions, such as hypertension and obesity. Over the last several years, numerous reports have demonstrated the in vitro and in vivo insulin-like activity of vanadate salts. Particularly, vanadate has been shown to stimulate glucose uptake and glycogen synthase activity in hepatocytes, adipocytes, diaphragm and skeletal muscle. Recently, we have demonstrated that the oral administration of vanadate salts improves glucose tolerance and completely normalizes insulin- mediated glucose uptake in diabetic animals, primarily through the stimulation of skeletal muscle glycogen synthesis. These and other previous observations support the hypothesis that this trace element can potentiate insulin action at the cellular level and that trace element therapy, either alone or in combination, may prove effective in the treatment of human diabetes mellitus. Insulin maintains glucose homeostasis by two major mechanisms: a) suppression of hepatic glucose production; b) stimulation of peripheral (muscle) glucose uptake. Once glucose is transported into the cell, it is phosphorylated to glucose 6- phosphate (G-6-P) and enters one of two major pathways, glycogen synthesis and glycolysis. In turn, glycolysis leads either to lactate formation or pyruvate oxidation in the Krebs cycle Recently, techniques have been developed to measure in vivo the rates of insulin-mediated glucose metabolism in humans. Thus, in the present study, we propose to examine the effect of the oral administration of vanadate on glucose tolerance, insulin-mediated glucose disposal, glucose oxidation, glycolysis and glycogen synthesis in healthy volunteers, IDDM and NIDDM subjects. This will be a placebo-controlled trial to obtain preliminary information regarding the short-term efficacy and safety of this trace element in human subjects.